The airway epithelium plays an important role in the inflammatory role of the lung by the formation of bioactive molecules such as eicosanoids. The epithelium serves as an air-liquid barrier for the trachea and bronchi and is a source of secretions including mucin. We are currently investigating the regulation of 15-lipoxygenase expression and activity by several inflammatory cytokines. For example, IL4 increases the expression of 15-lipoxygenase in both squamous and mucociliary cells. However, only in the mucociliary cells was a very dramatic increase in 15-lipoxygenase-1 expression produced. IL-4 is reported to be an important inflammatory mediator in lung. We are now determining if 15-lipoxygenase metabolites influence the formation of mucus. The addition of IL-4 decreases the formation of mucus and the expression of several mucus related genes (Muc-5, Muc-5 a/c) suggesting that the expression of 15-lipoxygenase may down regulate of attenuate mucus formation. The human cells may be the best model to investigate the pulmonary inflammatory processes and the role of lipid mediators. However, additional experiments are required to determine if 15-LO modulates mucin secretion. These studies indicate an importance of 15- Lipoxygenase in human lung inflammatory responses. - 15-LO, COX-1,2, airway inflammation, mucin secretion, cell differentiation